crossing96/oncoscreening huggingface dataset:
Complications and oncologic outcome in bladder cancer patients receiving radical cystectomy after intravesical instillation treatment.	OBJECTIVE: To evaluate the impact of previous intravesical treatment with Bacillus Calmette-Guérin (BCG) or mitomycin on postoperative complications and oncologic outcome in non-muscle invasive bladder cancer (NMIBC) patients receiving radical cystectomy (RC). PATIENTS AND METHODS: Between 2016 and 2021, 366 patients who received RC for bladder cancer (BC) were screened. Patients with intravesical treatment with either BCG or mitomycin for NMIBC were compared to patients with BC without prior intravesical treatment. Patients were matched manually for ASA-score, BMI cluster, age, and sex. TNM stages were used as covariates in the analysis model. All complications within 30 days post-surgery and the 90-day mortality rates were analyzed. Patient characteristics were compared between groups using Chi2-tests, and associations were evaluated by logistic regression. Firth logistic regression was applied for comorbidities. Kaplan-Meier curves were generated for overall survival (OS) and progression-free survival (PFS), and Cox regression analysis was performed to further assess survival outcomes. RESULTS: We identified 51 matched patients receiving BCG or mitomycin for NMIBC. Nine women and 42 men were in the interventional group with a mean age of 70 and a BMI of 27.6. In both groups, ASA-score 2, 3, and 4 were present in 18, 29, and four patients. According to the Clavien-Dindo (CD) classification grade ≥ 3b, neither the incidence nor severity of complications differed significantly between groups. Final histopathology and survival outcomes (OS, PFS) were comparable. No associations were found between complications and urinary diversion or surgical approach. As expected, advanced T- and N-stages correlated with worse survival, while coronary artery disease (CAD) was significantly associated with postoperative complications. CONCLUSIONS: To our knowledge, this is the first matched pair analysis that evaluates the impact of intravesical treatment on postoperative complications for patients with NMIBC receiving RC. Intravesical treatment with BCG or mitomycin did not deteriorate postoperative complications in NMIBC patients after RC, irrespective of the final histopathology stage. Oncologic outcomes were similar in both groups.	bladder
Diseases burden and trends of bladder cancer attributable to behavioral and metabolic factors among global and Chinese population, 1990-2021: results from the global burden of disease study 2021.	BACKGROUND: Behavioral and metabolic factors, such as smoking and high fasting plasma glucose (FPG), have been recognized as important risk factors for bladder cancer. This study aims to assess the global and Chinese burden of bladder cancer attributable to these factors and analyze long-term trends. METHODS: Data from the Global Burden of Disease (GBD) 2021 study were used. Indicators such as the number and rate of deaths and disability-adjusted life years (DALYs) were used to elucidate the disease burden. Joinpoint regression analysis and age-period-cohort models were applied to assess changes in the disease burden over different periods and the independent effects of age, period, and birth cohort. RESULTS: From 1990 to 2021, the global burden of bladder cancer attributable to smoking increased, with a decrease in the age-standardized mortality rate (ASMR) and age-standardized DALY rate (ASDR) by 38.09% and 40.78%, respectively. The global burden attributable to high FPG showed a rising trend in ASMR and ASDR, with percentage increases of 20.96% and 15.79%, respectively. In China, smoking-related trends were similar to the global pattern, but high FPG data showed more fluctuation. The age-period-cohort model showed increasing burden with age, except in the very elderly. Smoking-related burden decreased significantly across different periods and birth cohorts. For high FPG, the trend in China was more volatile. The risk was higher in earlier birth cohorts, followed by gradual improvement, but a recent rebound in risk was observed in the latest cohorts. The global cohort effect remained relatively stable. CONCLUSIONS: This study, based on GBD 2021, highlights the significant impact of behavioral and metabolic factors on bladder cancer burden globally and in China, with differing trends. China should strengthen tobacco and blood glucose management, focus on targeted interventions for the elderly, and enhance health education for the younger population to improve public health.	bladder
External validation of the Uromonitor®-version 2 urine test as a biomarker for optimisation of non-muscle-invasive bladder cancer management.	OBJECTIVES: To conduct an external multicentre validation to evaluate Uromonitor®-version 2 (v2; U-monitor, Porto, Portugal) as a biomarker for detecting non-muscle-invasive bladder cancer (NMIBC) recurrence in an independent patient cohort in a real-world-evidence setting and compare it to cytology. PATIENTS AND METHODS: The 'External Validation of Uromonitor as a Biomarker for Optimization of NMIBC Management by the Club Urológico Español de Tratamiento Oncológico Group' (EVALUATION-CUETO) study is a prospective, multicentre, observational study (NCT05864599) conducted in Spain. Inclusion criteria included any risk group of patients with NMIBC undergoing follow-up. The most recent (index) NMIBC tumours of any grade had to have been diagnosed within the past 3 months to 2 years. Regarding biomarkers, data from cystoscopy, cytology, and the Uromonitor-v2 test were collected. Predictive performance parameters, including accuracy, area under the curve, negative and positive predictive values (NPV, PPV), sensitivity, and specificity, were calculated. RESULTS: A total of 1178 patients with a mean age of 72 years and a predominant male representation (80%) were included. Among the positive Uromonitor-v2 cases, 64 (57.66%) exhibited a TERT promoter mutation, and 59 (53.15%) harboured a FGFR3 mutation. No KRAS mutations were found. For the total population, Uromonitor-v2 demonstrated high specificity (0.93) and NPV (0.93), but low sensitivity (0.36) and PPV (0.36), indicating a limited ability to detect all recurrences and confirm positive cases. Performance varied across tumour grades, with low-grade tumours showing a low sensitivity of 0.32 and high-grade tumours achieving a higher but insufficient sensitivity of 0.44. Specificity remained consistent at 0.93 across all groups. Uromonitor-v2 achieved higher accuracy compared to cytology alone, with the combined approach further improving overall predictive performance. CONCLUSION: The strong specificity and NPV observed across all studies suggest a role of Uromonitor-v2 as a potential tool for NMIBC follow-up, particularly in ruling out recurrence and clarifying doubtful cystoscopy results. However, the unexpectedly low sensitivity reported in this external multicentre validation suggests the need for further investigation before routine clinical implementation.	bladder
The integration of transcriptomics and metabolomics elucidates the antitumor mechanisms of mycophenolic acid in bladder cancer cells.	The potential anticancer effects of mycophenolic acid (MPA), an inosine-5'-monophosphate dehydrogenase (IMPDH) inhibitor, and its ability to prolong survival have been suggested. However, the comprehensive impact of MPA on bladder cancer remains unclear. Our results demonstrate that MPA induces both ferroptosis and apoptosis in human bladder cancer cells. To investigate the underlying mechanisms, we employed integrated transcriptomic and metabolomic analyses. Our analysis revealed that differentially expressed genes (DEGs) are primarily implicated in the regulation of metabolism, inflammatory responses, and angiogenesis. Metabolomic profiling identified phosphocreatine, 2'-CMP, CDP, and others as differentially accumulated metabolites (DAMs). Integrated analysis of differentially expressed genes (DEGs) and differentially abundant metabolites (DAMs) demonstrated that MPA significantly alters the metabolism of key compounds (GMP, phenol, glutathione, NAD+, cytosine) and regulates critical genes (tyrosine, LDHA, LDHB). Notably, the dysregulation of genes and metabolites associated with reactive oxygen species (ROS)-related pathways may serve as a central mechanism by which MPA facilitates ferroptosis and apoptosis in bladder cancer.	bladder
Impact of timing between neoadjuvant therapy and radical cystectomy on survival in muscle-invasive bladder cancer.	INTRODUCTION: Previous studies investigated the impact of timing between neoadjuvant therapy (NAT) and radical cystectomy (RC) (NAT-to-RC interval) on overall survival (OS). However, these studies primarily focused on neoadjuvant chemotherapy (NAC), leaving the effects of neoadjuvant immunotherapy (NAI) and chemoimmunotherapy (NACI) unexplored. METHODS: We retrospectively reviewed 717 treated with RC between 2015 and 2024 at a tertiary referral center. For the purpose of the study, patients receiving either NAC, NAI, or NACI were included. Multivariable Cox regression analysis (MCR) was used to assess the association between the NAT-to-RC interval and any cause of death. MCRs models together with the Harrell's C-index, were used to test progressively increasing weekly NAT-to-RC interval cut-offs. Kaplan-Meier analysis was used to estimate OS based on the first interval threshold significantly associated with survival outcomes. RESULTS: Among 246 eligible patients, 110 (45%) received NAC, 101 (41%) NAI, and 35 (14%) NACI. The NAT-to-RC interval was 46 days (IQR: 28-71 days). Over a median follow-up of 40 months, 43 patients (17%) died from any cause. In MCR, longer NAT-to-RC intervals were significantly associated with reduced OS (per 2-week increase: Hazard ratio [HR] 1.06, p = 0.004). The first statistically significant cut-off was at 11 weeks (adjusted HR: 1.88, p = 0.048, C-index: 74%). Patients with an interval of 11 weeks or more (n = 53, 22%) had significantly lower 3-year OS than those with shorter intervals (86% vs. 75%, adjusted HR: 1.88, p = 0.048). Similar results were observed in the NAI/NACI subgroup with a 14-week cut-off (unadjusted HR: 4.27, p = 0.043, C-index: 59%). CONCLUSION: A prolonged NAT-to-RC interval is independently associated with poorer OS, even in patients receiving NAI or NACI. An interval of 11 weeks is associated with a decline in OS, suggesting a potential time-sensitive impact of delayed RC. These findings underscore the importance of timely RC following NAT, particularly as the use of NAT strategies continues to expand.	bladder
A case-based review of urachal carcinoma with mixed small cell neuroendocrine and adenocarcinoma components, with one new case report and analysis of nine published cases.	INTRODUCTION: Urachal carcinoma (UrC) is an uncommon malignant neoplasm arising from urachal remnants and represents only 0.01%-0.7% of bladder cancers. Adenocarcinoma-usually of the intestinal type-accounts for over 80% of cases, whereas neuroendocrine carcinoma (NEC) is exceedingly rare. Fewer than ten cases of urachal NEC have been documented in the English-language literature, most diagnosed at advanced stages with poor outcomes. We report an additional case and review published data to enhance clinical recognition and management of this ultra-rare tumor. CASE PRESENTATION: A 43-year-old woman presented to Shandong Provincial Hospital, Shandong First Medical University, after a urachal midline mass was incidentally detected on routine health examination. Preoperative tests showed a CEA level of 7.28 ng/mL. CTU revealed a 3.9 × 2.7 × 2.4 cm cystic-solid lesion at the anterior bladder wall, suspicious for urachal malignancy. Cystoscopic biopsy confirmed small-cell NEC. The patient underwent laparoscopic urachal resection with umbilicus preservation, extended partial cystectomy, and bilateral pelvic lymphadenectomy. Postoperative pathology showed a mixed urachal carcinoma composed of ~80% small-cell NEC and ~20% adenocarcinoma, forming a 4.5 × 3 × 1.5 cm cystic-solid mass. Margins and lymph nodes were negative. Immunohistochemical analysis showed a high Ki-67 labeling index (80%) and positive staining for synaptophysin (Syn), chromogranin A (CgA), insulinoma-associated protein 1 (INSM1), cytokeratin 20 (CK20), and mutant-pattern p53. Retinoblastoma protein (RB) and GATA-3 were negative. The patient received four cycles of adjuvant etoposide-cisplatin (EP) chemotherapy. Surveillance with tumor markers and whole-abdominal CT every three months showed no evidence of recurrence at the 8-month follow-up. CONCLUSION: Urachal NEC with mixed small-cell and adenocarcinoma components is an exceptionally rare and highly aggressive malignancy lacking standardized diagnostic or therapeutic guidelines. Complete surgical excision with negative margins remains the mainstay of treatment, while adjuvant regimens are typically adapted from small-cell carcinoma protocols of the lung or urinary tract. We report a case managed with umbilicus-sparing urachectomy and extended partial cystectomy followed by EP chemotherapy, together with a review of nine previously published cases. These findings provide literature-based evidence to guide individualized management and inform future multidisciplinary research.	bladder
Evaluating the reliability of large language models for clinical data extraction in bladder cancer prognosis.	Advances in natural language processing (NLP) and machine learning could assist human users in clinical data extraction from unstructured electronic medical records (EMRs). This study investigates the accuracy and consistency of several Large Language Models (LLMs) - including Dolly, Vicuna, Llama, and GPT-4 - in extracting critical clinical information pertinent to bladder cancer survival prediction. Using EMRs from 163 bladder cancer patients, we assessed the impact on LLM performance by factors such as differences in the trained models, model evolution, input text length, and sequencing of case inputs. GPT-4 demonstrated superior performance with Fleiss' Kappa values exceeding 0.97, accuracy consistently above 93%, and survival prediction metrics closely aligned with ground truth (AUC ± 0.02). Among offline models, Llama-2.0-13b and Llama-3.3-70b exhibited the highest reliability in both information extraction and survival prediction. This study underscores the potential of LLMs to automate clinical data extraction for predictive modeling while highlighting the challenges related to LLM variability and reliability.	bladder
Integrative multi-omics and single-cell transcriptomics reveal ARHGEF12 driving chemoresistance in bladder cancer.	Bladder cancer (BLCA) is the predominant type of urothelial carcinoma in urinary system, and resistance to cisplatin-based chemotherapy substantially worsens clinical outcomes, presenting a major therapeutic obstacle. In this study, we integrated genome-wide association study (GWAS) data with expression quantitative trait loci (eQTL) analyses, and applied Mendelian randomization (MR) to assess the causal effects of eQTLs from 19,942 genes on BLCA. By incorporating scRNA-seq data, our study also identifies differentially expressed genes (DEGs) in cisplatin-resistant BLCA cells and examined their causal associations with BLCA, aiming to elucidate genetic drivers of chemoresistance and tumor progression. Through this integrated approach, we identified the eQTL of the ARHGEF12 gene as a key mediator of cisplatin resistance. Bioinformatic analysis revealed that elevated ARHGEF12 expression was strongly associated with activation of the PI3K/Akt signaling pathway. To define ARHGEF12's role in cisplatin resistance, we established a cisplatin-resistant UM-UC-3/DDP model. Silencing ARHGEF12 markedly reduced chemoresistance, increased apoptotic cell death, and induced pronounced morphological changes. Pharmacological modulation with the ROCK inhibitor Y-27632 and a rescue assay with the Akt activator SC79 supported a model in which ARHGEF12 drives chemoresistance via RhoA/ROCK-dependent activation of the PI3K/AKT axis. This study is the first to integrate MR with single-cell transcriptomics to explore the genetic contribution to cisplatin resistance in BLCA. Our results uncover a novel mechanistic role of ARHGEF12 in BLCA progression and chemoresistance and suggest it as a potential therapeutic target for precision treatment strategies.	bladder
Basal subtype of invasive urothelial carcinoma of the bladder has aggressive behavior and poor prognosis: An immunohistochemistry-based study.	INTRODUCTION: Molecular subtyping of urothelial cancer of the bladder can help in identifying aggressive subtypes and aid in the prognostication of the disease. These subtypes can be broadly identified with the help of immunohistochemistry (IHC) markers reliably. AIMS: To assess the molecular subtypes of urothelial carcinoma of the bladder using IHC markers and evaluate their association with clinicopathological characteristics and overall survival (OS). MATERIALS AND METHODS: This was a cross-sectional study done over 3 years in a tertiary care center. There were 109 cases of invasive urothelial carcinoma of the bladder. In 43 cases, radical cystectomy was performed, and 66 cases underwent transurethral resection of bladder tumor. CK5/6, and CK14 were used as markers of the basal subtype; GATA-3 and CK20 were used for the luminal subtype. Cases were classified into basal, luminal, double-positive, and double-negative subtypes. The association of molecular subtypes with clinicopathological characteristics was analyzed. OS was analyzed for the molecular subtypes. All the relevant statistical tests were performed using IBM SPSS software version 24.0. RESULTS: The most frequently occurring molecular subtype was luminal (GATA3+, CK5/6-) in 62% of cases. Tumors with the basal subtype showed a higher frequency of muscle invasion compared to nonbasal types and presented as high-grade tumors. The luminal subtype was significantly associated with conventional histology and lamina propria invasive tumors. The basal molecular subtype showed a mean OS of 15 (±4) months, which was significantly worse than that of nonbasal subtypes. CONCLUSION: The basal subtype of urothelial carcinoma of the bladder behaves more aggressively in terms of grade, extent of invasion, and OS.	bladder
High-dose vitamin C improves BCG immunotherapy's efficacy in a murine ectopic model of bladder cancer.	Management of non-muscle-invasive bladder cancer (NMBIC) typically involves transurethral resection of bladder tumor (TURBT) followed by intravesical Bacillus Calmette-Guérin (BCG) immunotherapy. However, 30-50 % of patients may not respond to BCG or experience recurrence. High-dose vitamin C (VitC) has shown promise in improving the outcome of immunotherapies such as immune checkpoint blockade. However, evidence of its ability to augment BCG immunotherapy in bladder cancer remains lacking. Tumor-bearing male C57BL/6 mice were divided into four treatment groups receiving placebo, BCG, VitC, and BCG/VitC, respectively. After 22 days, tumors were collected and subjected to histopathological evaluation using H&E staining. Expression of CD4, CD8, NK1.1, F4/80, CD80, CD163, and Ki67 in the tumor microenvironment was assessed by immunohistochemistry (IHC). mRNA levels of Th1 cytokines (IL-2, IL-12, IFNG, TNFA), Th2 cytokines (IL-4, IL-5, IL-6, IL-10), and NOS2 were determined using qPCR. Serum levels of IL-12 and TNF-α were quantified using enzyme-linked immunosorbent assay (ELISA). The results demonstrated that VitC remarkably improves the efficiency of BCG immunotherapy. The combination of BCG and VitC resulted in greater inhibition of cell proliferation, reduced tumor sizes, and increased infiltration of inflammatory cells compared to BCG monotherapy, indicating a synergistic effect on the antitumor immune responses. Additionally, BCG/VitC treatment led to a predominance of M1 macrophages and a substantial increase in the infiltration of natural killer cells, as well as T-lymphocytes. Furthermore, mice receiving combination therapy exhibited the highest levels of intratumoral Th1 cytokines while decreasing Th2 cytokines. In conclusion, VitC appears to play a critical role in enhancing BCG-mediated immune responses against NMBIC.	bladder
National and subnational trends of years of life lost and reduced life expectancy caused by bladder cancer in China from 2005 to 2020.	BACKGROUND: Bladder cancer was commonly diagnosed cancer, which has a high disease burden in China and the world. This study aims to better assess the epidemiological situation of bladder cancer in China. METHODS: Data for bladder cancer mortality were observed based on the data from the National Mortality Surveillance System. We analyzed the number of deaths, years of life lost(YLL), the age-standardized mortality rates(ASMR) and the age-standardized YLL rates due to bladder cancer in China during 2005-2020. We calculated the reduction in life expectancy due to bladder cancer. RESULTS: In 2020, bladder cancer accounted for 29 730 deaths and 492 859 YLL in China. The ASMR and the age-standardized YLL rate of males were consistently higher than that of females. From 2005 to 2020, the reduction in life expectancy due to bladder cancer increased from 0.018 to 0.021 years. The reduction in life expectancy caused by bladder cancer in urban areas was consistently higher than that in rural areas, since this increased from 0.013 years in 2005 to 0.018 years in 2020 in rural areas. The reduction in life expectancy caused by bladder cancer in males was higher than that in females, and increased from 0.024 to 0.029 years in males between 2005 and 2020. CONCLUSIONS: The number of deaths for bladder cancer in China has been increasing in recent years. Although the loss of life expectancy caused by bladder cancer in China was relatively small, the gradually increasing trend warrants attention, especially in economically developed regions.	bladder
HLA class-I genotyping to personalize Bacille Calmette-Guerin immunotherapy in bladder cancer.	Bacille Calmette-Guerin (BCG) is the immunotherapy of choice for high-risk non-muscle invasive bladder cancer (BC), although recurrence eventually occurs in 50% of patients and 20% progress to advanced stages. This study evaluates the predictive value of human leukocyte antigen class-I (HLA-I) genotyping to guide BCG immunotherapy. HLA-I genotyping and expression of NK cell receptors in circulating T and NK lymphocytes was evaluated at diagnosis in 325 consecutive BC patients (151 treated with BCG and 174 with other therapies), 648 patients with other cancers and 23,250 healthy controls. Proliferation, cytotoxicity, and production of cytokines and intracellular nitric oxide (icNO) was assessed in peripheral blood mononuclear cells from these donors, selected based on their Bw4 genotype, after stimulation in vitro with anti-CD3/CD28 or BCG. HLA-A*11, HLA-B*07 and HLA-B*18 allotypes were associated with favorable outcomes after BCG therapy (longer progression-free and overall survival), whereas HLA-B*44 and other KIR3DL1 Bw4 ligands were associated with unfavorable outcomes. Although Bw4 ligands were associated with better NK cell education in vivo (CD226-upregulation, KIR3DL1 downregulation and stronger NK cytotoxic capacity), they were also associated with weaker NK cell proliferation, and lower IL-1β, IL-6, and icNO production after BCG stimulation in vitro, revealing an inhibitory role of KIR3DL1. Mechanisms by which KIR3DL1/Bw4 interaction interferes with BCG-induced NK cell proliferation and the production of cytokines and icNO, warrant further investigation. HLA-I genotyping should be investigated as a useful biomarker to personalize BCG immunotherapy in BC.	bladder